OBJECTIVE: Multiple myeloma (MM) is a B-cell malignancy characterized by the clonal proliferation of malignant plasma cells.According to results of some studies, it has been suggested that the HLA class 1 and 2 genes have susceptibility effects on MM. Studies of different populations have reported different HLA class 1 and 2 alleles that affect MM. In this study, we assessed the association of HLA class 1 and class 2 antigens with MM in Iranian patientsMETHODS: We performed a case-control genotyping study with 105 Iranian MM patients that were selected from the bone marrow transplantation department of Taleghani Hospital and 150 controls using single specific primerpolymerase chain reaction with the HLA-Ready Gene ABDR Kit.RESULTS: Our results demonstrated that 21% of patients versus 12% of controls and 11% of patients versus 3% of controls carried HLA-A*03 and HLA-B*18, respectively. The MM patients had a significant increase in the frequency of HLA-A*03 and HLA-B*18 alleles in comparison to control subjects (p=0.039, OR=2.057 and p=0.013, OR=3.567, respectively).CONCLUSION: Our findings suggested that the HLA-A*03 and HLA-B*18 alleles have significant susceptibility effects on MM in the Iranian population. However, compared to other populations, the above-mentioned alleles had different statuses. Since there are not many studies evaluating and calculating this association among ethnic groups, further studies among other populations are needed to explain the exact association of the HLA genes with MM.